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- Ahmad, Shafqat, et al.
(author)
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Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome : A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study
- 2022
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In: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 71:2, s. 329-339
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Journal article (peer-reviewed)abstract
- Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.
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- Andersson, Claes, et al.
(author)
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Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway
- 2020
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Journal article (peer-reviewed)abstract
- We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.
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- Banyoi, Silvia-Maria, et al.
(author)
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The effects of exposure to environmentally relevant PFAS concentrations for aquatic organisms at different consumer trophic levels : Systematic review and meta-analyses
- 2022
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In: Environmental Pollution. - : Elsevier. - 0269-7491 .- 1873-6424. ; 315
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Research review (peer-reviewed)abstract
- Per-and polyfluoroalkyl substances (PFAS) is a collective name for approximately 4700 synthetic chemicals ubiquitous in the aquatic environment worldwide. They are used in a wide array of products and are found in living organisms around the world. Some PFAS have been associated with cancer, developmental toxicity, endocrine disruption, and other health effects. Only a fraction of PFAS are currently monitored and regulated and the presence and effects on aquatic organisms of many PFAS are largely unknown. The aim of this study is to investigate the health effects of environmentally relevant concentrations of PFAS on aquatic organisms at different consumer trophic levels through a systematic review and meta-analysis. The main result shows that PFAS in concentrations up to 13.5 μg/L have adverse effects on body size variables for secondary consumers. However, no significant effects on liver or gonad somatic indices and neither on fecundity were found. In addition, the results show that there are large research gaps for PFAS effects on different organisms in aquatic environments at environmentally relevant concentrations. Most studies have been performed on secondary consumers and there is a substantial lack of studies on other consumers in aquatic ecosystems.
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- Dixon, Tülay, et al.
(author)
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Toward an empirical understanding of formality: Triangulating corpus data with teacher perceptions
- 2023
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In: English for specific purposes (New York, N.Y.). - : Elsevier. - 0889-4906 .- 1873-1937. ; 71, s. 161-177
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Journal article (peer-reviewed)abstract
- Academic writing is often referred to as “formal,” but the teaching and assessment of formality can be challenging as formality has been conceptualized in many ways. The goal of this study is to explore the elusive construct of formality in the context of academic writing, especially with regard to what formality means to academic writing instructors. We used instructors’ perceptions of formality (i) to identify relationships between the use of linguistic features in academic texts and perceptions of formality and (ii) to determine the extent to which the situational characteristics of texts (e.g., differences in audience, purpose, and discipline) are related to perceptions of formality. Specifically, we asked 72 academic writing instructors to rate the formality level of 60 short academic text excerpts on a five-point scale. The excerpts were sampled from two publication types (university textbooks, journal articles) in three disciplines (psychology, biology, history). Overall, the results indicate that perceptions of formality can be explained by both linguistic features and situational characteristics. As linguistic features and situational characteristics are intertwined, differences in perceptions of formality seem to be functionally motivated. Implications for the teaching of academic writing are discussed.
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